title: Contribution of extrahepatic small cells resembling small hepatocyte-like progenitor cells to liver mass maintenance in transplantation model of retrorsine-pretreated liver.
abstract: OBJECTIVE
  Retrorsine selectively inhibits hepatocyte proliferation and following liver injury evokes small hepatocyte-like progenitor cells. The aim of this study is to find out whether endogenous extrahepatic cells contribute to small hepatocyte-like progenitor cells after retrorsine treatment.
  
  
  METHODS
  Wild-type Lewis rat liver exposed to retrorsine was transplanted into GFP transgenic Lewis rat. GFP positive, albumin-producing polygonal cells were expected as reciepient-derived hepatocyte-like cells.
  
  
  RESULTS
  Four weeks after transplantation of 50% volume of retrorsine-pretreated liver, the rate of GFP positive hepatocyte-like cells was 0.02365%. Majority of these cells resided as single cells and their cell size was significantly larger than that of normal hepatocytes (mean cell size; 799.4 um(2) vs. 451.3 um(2), p<0.0001). At eight weeks, clusters of GFP positive small-size albumin-producing cells appeared and occupied 0.00759% of hepatocytes. The morphology of these cells was similar to that of small hepatocyte-like progenitor cells, 12.5% of them were Ki67 positive, majority of them were negative for CYP1A2 staining, and some clusters contained larger cells indicating further maturation.
  
  
  CONCLUSIONS
  Endogenous extrahepatic cells can form a cluster of small cells resembling small hepatocyte-like progenitor cells in a transplanted retrorsine-pretreated liver. The contribution of extrahepatic cells to liver mass maintenance is quite low and its importance is unclear.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research 771, Baltimore, MD 21205 USA ; Department of Surgery and Cancer Treatment Center, Kochi Medical School, Kohasu Oko-cho, Nankoku-city, Kochi, 783-8505 Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Maeda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ota
authors.forename: Yongchung
authors.initials: Y
authors.lastname: Wang
authors.forename: Kalyani
authors.initials: K
authors.lastname: Ramachandran
authors.forename: Robert A
authors.initials: RA
authors.lastname: Montgomery
authors.forename: George Melville
authors.initials: GM
authors.lastname: Williams
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Sun
keywords: GFP; Liver transplantation; Retrorsine; SHPC